1. Field of the Invention
This invention is directed to crystalline forms of 1-methylcarbapenem derivatives or of pharmaceutically acceptable salts thereof which exhibit excellent antibiotic activity against various bacterial strains and are stable enough to keep for a long time.
This invention is directed compositions for the prevention or treatment of bacterial infections containing a crystalline form of the present invention as an active ingredient.
This invention is directed to uses of a crystalline form of the present invention in order to prepare a medicament for the prevention or treatment of bacterial infections.
This invention is directed to methods for the preventing or treating bacterial infections which comprise administering to a warm-blooded animal in need of such prevention or treatment an effective amount of a crystalline form of the present invention.
Further this invention is directed to processes for the preparation of crystalline forms of the present invention.
2. Description of Related Art
The 1-methylcarbapenem derivative of formula (I) is disclosed in Japanese Patent Application Publication Hei-10-204086 and Hei-11-071277 and in U.S. Pat. No. 6,090,802 (corresponds to Hei-10-204086). This compound (I) exhibits excellent antibiotic activity not only against Gram-positive bacterial strains but also against Gram-negative bacterial strains and can be expected to become a useful antibiotic agent. However, the compound (I) prepared according to the Example of Japanese Patent Application Publication Hei-11-071277 (which is Example 72 of U.S. Pat. No. 6,090,802) was obtained by lyophilization as a non-crystalline powder. This powder is unstable and is a material difficult to keep for a long time. There are many problems in practical use of the powder as a medicament, especially as an antibiotic agent. The inventors made many efforts in order to solve these problems and have found that certain crystalline forms of compound (I) are extremely stable compared to the non-crystalline powder of compound (I) and are useful medicaments, especially, practically useful antibiotic agents. The stable crystalline forms of this invention include a crystalline form of compound (I) containing 3 hydrate and 1 ethanol (I-1), a crystalline form of compound (I) containing ½ ethanol (I-2), a crystalline form of compound (I) and a crystalline form of compound (I) containing ¼ ethanol and 3/2 water (I-3).